In the fermentative production of an amino acid generally using a microorganism belonging to the genus Escherichia or a microorganism such as a coryneform bacterium, as typified by the genus Corynebacterium, glucose serves as the main raw material to supply carbon for both the growth of the microorganism and the production of the amino acid.
While glucose is metabolized to various compounds mainly via the glycolytic system and the pentose phosphate pathway, the metabolism involving carbon is known to include gluconeogenesis that reverses the glycolytic system; when a microorganism grows using a carbon source like acetic acid, for example, the necessary metabolites for the growth must be biosynthesized via the gluconeogenetic pathway. Hence, the metabolism from glucose is expressed as the sum of both the metabolic pathways of glycolysis and gluconeogenesis.
Gluconeogenesis is necessary for microorganisms to survive in various environments, and it is known that the balance between the glycolytic system and gluconeogenesis is regulated according to environmental factors. It has been reported that in microorganisms belonging to Escherichia coli, the glycolysis/gluconeogenesis balance is regulated mainly by the Csr (Carbon Storage Regulator) system (non-patent document 1). It is a regulatory protein known as CsrA protein that plays the central role in the Csr system, having the function of binding to the 5′-noncoding region of target messenger RNA to increase the translation of glycolytic system enzymes and reduce the translation of gluconeogenesis enzymes. Recently, deficiency of the csrA gene was reported to improve L-phenylalanine productivity, and this is attributed to enhancement of the shikimic pathway, which is essential for L-phenylalanine production, as a result of an increased supply of phosphoenolpyruvic acid due to decreased glycolysis and increased gluconeogenesis (non-patent document 2).
Meanwhile, it is known that the Csr system includes, as regulatory factors, CsrB RNA (non-patent document 3) and CsrC RNA (non-patent document 1) which bind to CsrA protein to reduce its function. CsrB RNA and CsrC RNA are both noncoding small RNAs, and are known to have, as CsrA protein binding sites, 18 and 9 conserved nucleotide sequences comprising the nucleotide sequences shown by SEQ ID NO:1, 2 and 3, respectively.
However, to date, it has not been reported that amino acid productivity was improved by modifying, particularly deleting, a function of a small RNA involved in the regulation of the glycolytic system/gluconeogenesis balance, such as CsrB RNA or CsrC RNA.
Non-patent document 1: Journal of Bacteriology, 1993, vol. 175, p. 4744-4755
Non-patent document 2: Current Microbiology, 2001, vol. 43, p. 26-32
Non-patent document 3: The Journal of Biological Chemistry, 1997, vol. 272, p. 17502-17510